title: Milnacipran inhibits itch-related responses in mice through the enhancement of noradrenergic transmission in the spinal cord.
abstract: We investigated whether milnacipran, a serotonin-noradrenaline reuptake inhibitor, exhibits an antipruritic effect through the spinal action in mice. Intrathecal injections of milnacipran (0.1 - 10 μg/site) significantly suppressed serotonin-induced biting, which is an itch-related response. However, such an effect was not observed with fluvoxamine (10 μg/site), which is a selective serotonin reuptake inhibitor. Furthermore, an intraperitoneal injection of milnacipran (10 mg/kg) inhibited serotonin-induced biting. When phentolamine (1.0 μg/site), a non-selective α-adrenoceptor antagonist, was intrathecally injected, it inhibited the above response of milnacipran. These results suggest that milnacipran suppresses itching through the inhibition of noradrenaline reuptake in the spinal cord.
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Gotoh
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kuraishi
mesh_terms: D018759:Adrenergic Uptake Inhibitors; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000982:Antipruritics; D003521:Cyclopropanes / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000078764:Milnacipran; D009638:Norepinephrine / Q000502:physiology*; D010646:Phentolamine / Q000008:administration & dosage / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors; D013116:Spinal Cord / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000317:Adrenergic alpha-Antagonists; D000982:Antipruritics; D003521:Cyclopropanes; D000078764:Milnacipran; D009638:Norepinephrine; D010646:Phentolamine; D017367:Selective Serotonin Reuptake Inhibitors